1. Introduction This is an R21 proposal to conduct a clinical trial which will test the use of a safe and minimally invasive dietary intervention to enhance the removal of toxic polychlorinated biphenyls (PCBs) from individuals with elevated levels of these compounds. To conduct this study, we will enroll subjects in Anniston, Alabama, a community in which a significant portion of the local population has been exposed to PCBs as a result of contaminated commercial waste. Many of the residents of Anniston currently have markedly elevated blood and adipose tissue PCB levels. In addition, these individuals have a several-fold increased prevalence of type-2 diabetes and are potentially at greater risk of other health disorders. Due to previous research and litigation, Anniston residents are already aware of environmental PCB contamination in their community and the associated risk for adverse health effects resulting from this exposure. We have pioneered a method for adding a small amount of non-absorbable fat to the diet for use as a therapeutic tool which hastens the elimination of persistent lipophilic compounds, such as PCBs, in a safe manner. Our rationale is based on the fact that once PCBs and other organochlorine pollutants enter the body, they circulate among several organs including the small intestine. Under normal circumstances, these compounds are reabsorbed from the intestine and returned to the blood, and are thus prevented from being excreted in the feces. The addition of a small amount of non-absorbable lipid in the diet provides a matrix for physically retaining the pollutants within the intestinal lumen, which then allows the pollutants to be excreted along with the lipid. Although the excretion on any given day is relatively small, the cumulative excretion over the course of a year becomes clinically significant. The Anniston population provides an ideal population to assess this intervention in a meaningful way, and we have allied with a local community group to assist in the recruitment of subjects and to carry out the relatively simple dietary manipulations required for this study. We will carry out a double-blind, placebo controlled study of a non-absorbable fat in subjects known to have elevated levels of PCBs. We will measure the rate of change of the blood levels of PCBs in these subjects. PUBLIC HEALTH RELEVANCE: Project Narrative We will carry out a double-blind, placebo controlled study in Anniston, Alabama in subjects previously shown to have elevated body burdens of PCBs. We will determine the efficacy of non-absorbable dietary lipid in reducing PCB levels by interrupting enterohepatic circulation of PCBs and their lipophilic metabolites. A positive outcome will offer a treatment option for the potential reduction of the risk of disease in subjects exposed to PCBs and other persistent organic pollutants.